Cushing syndrome (CS), a fatal disease, is suspected in many thousands of patients each year, but confirmed in only a fraction of these. This project seeks to identify accurately which patients have Cushing syndrome, to define the etiology of their disease and to treat it optimally. A major goal during the past year was to better delineate, through the use of a validated survey instrument, the subjective quality of life of patients before and after treatment of Cushing syndrome. We want to delineate the subjective experience of hypercortisolism and the recovery period, and to evaluate whether patterns of response predict a later pattern of recovery. We use the entire SF-36 questionnaire developed by John Ware and colleagues, as a subset of the larger questionnaire administered in the Medical Outcomes Study. Since the SF-36 does not delineate areas related to social function, memory and cognition very well, we have added other questions in these domains taken from the Medical Outcomes Study. Patients also complete a symptom checklist and a questionnaire about recurrence, satisfaction with treatment, current treatment, and demographics. Initial analysis suggests that patients with active Cushing syndrome have great impairment in physical activities and cognitive function and that they also limit social activities. There are also significant, but less profound abnormalities in the sense of well-being and general health perception and activities because of emotional problems are increased compared to the general population. Preliminary evaluation of patients after treatment suggests improvement in these areas, but some patients do not regain scores similar to the general population as long as five years after treatment, suggesting significant long-term impairment of quality of life in some individuals with Cushing syndrome An additional initiative was to evaluate the utility of salivary cortisol as a screening test for Cushing's syndrome. Measurement of salivary cortisol would theoretically be a useful non-invasive test. We evaluated 136 inpatients and 4 outpatients with possible Cushing's syndrome, 16 inpatients and 7 outpatients with other non-adrenal disorders, and 34 healthy outpatients. Using cutpoints that excluded all subjects without Cushing's syndrome, we compared the sensitivity for the detection of Cushing's syndrome of nighttime salivary cortisol levels (2330 and 0000 h for inpatients and bedtime for outpatients), simultaneous inpatient serum cortisol levels, and urine glucocorticoid excretion. An assay-specific inpatient midnight or an outpatient bedtime salivary cortisol > 550 ng/dL (15.2 nmol/L) identified 93% of patients with Cushing's syndrome (CI: 89-98%), and excluded all individuals without the disorder. Salivary cortisol measurements worked as well as plasma measurements, and better than urine glucocorticoid excretion. We conclude that bedtime salivary cortisol measurement is a practical and accurate screening test for the diagnosis of Cushing's syndrome.